Variant 2-190517530-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142645.2(NEMP2):c.602T>C(p.Phe201Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,549,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NEMP2
NM_001142645.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEMP2	NM_001142645.2 linkuse as main transcript	c.602T>C	p.Phe201Ser	missense_variant	5/9	ENST00000409150.8	NP_001136117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEMP2	ENST00000409150.8 linkuse as main transcript	c.602T>C	p.Phe201Ser	missense_variant	5/9	2	NM_001142645.2	ENSP00000386292	P1	A6NFY4-1
NEMP2	ENST00000414176.5 linkuse as main transcript	c.395T>C	p.Phe132Ser	missense_variant, NMD_transcript_variant	5/7	2		ENSP00000404283		A6NFY4-2
NEMP2	ENST00000343105.9 linkuse as main transcript	c.*183T>C		3_prime_UTR_variant, NMD_transcript_variant	5/6	4		ENSP00000340087
NEMP2	ENST00000444545.5 linkuse as main transcript	c.*183T>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	3		ENSP00000403867

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000450

AC:

AN:

155584

Hom.:

AF XY:

0.0000366

AC XY:

AN XY:

82042

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000251

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1396958

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

688962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000563

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000196

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.602T>C (p.F201S) alteration is located in exon 5 (coding exon 5) of the NEMP2 gene. This alteration results from a T to C substitution at nucleotide position 602, causing the phenylalanine (F) at amino acid position 201 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.39

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.13

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.050

Polyphen

0.93

Vest4

0.37

MutPred

0.76

Loss of stability (P = 0.0057);

MVP

0.43

ClinPred

0.91

GERP RS

-3.7

Varity_R

0.27

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over